The purpose of the present study is to determine the safety and tolerability and potential clinical efficacy of subcutaneous doses of recombinant human IL-10 (rHuIL-10) in patients with rheumatoid arthritis (RA). RA is a chronic inflammatory disease of unknown etiology. It is characterized by synovial inflammation with frequent progression to articular cartilage and bone destruction. The synovial inflammatory response in RA consists predominately of T lymphocytes, mostly T helper cells (Th), with fewer numbers of macrophages and B lymphocytes. The Th cells can be divided into two overlapping subpopulations with important functional significance, Th1 and Th2 cells. Th1 cells secrete IL-2 and interferon- and regulate cell-mediated responses. Th2 cells secrete IL-4, IL-5, and IL-10, and mediate humoral responses. Most Th cells in the rheumatoid joint belong to the Th1 subpopulation. The synovial tissue in RA exhibits other features typical of a cell-mediated response, including hypervascularity, upregulation of cell adhesion molecules, and overexpression of pro-inflammatory cytokines such as IL-1 and tumor necrosis factor (TNF)-. IL-10, a cytokine produced by Th2 cells and macrophages, has primarily immunosuppressive and anti-inflammatory properties. The inhibitory effects of IL-10 have been observed in animal models of arthritis where treatment with this cytokine can ameliorate joint inflammation. The study is a phase II, multicenter, double-blind, placebo-controlled, clinical trial of rHuIL-10 therapy given daily (4 5g/d, 8 5g/d, or placebo) or three times week (8 5g/d, 20 5g/d or placebo) subcutaneously. The dosing period is twelve weeks for the randomized phase and an additional 12 weeks for the extension study. The main outcomes are the frequency and severity of adverse effects and the American College of Rheumatology Core Disease Measures. The study is ongoing. Thus far, our site has enrolled 3 patients (1 male and 2 females, 2 Caucasian / 1 Afro-American) with a planned total of 15 patients.